Cancers (malignant tumors) are one of the leading diseases threatening a human life today. The morbidity and mortality of the tumors have increased sharply in recent years, Tumor development trend revealed by the World Health Organization (WHO) indicates that the annual newly confirmed tumor patients in the world wide are more than 10,000,000 since 1996, the global total tumor patients had exceeded 40,000,000 by the end of 1999, and thus approximately 7,000,000 persons die of various tumors all over the world each year. In 2001, the morbidity and mortality of tumors in the world had increased by 22% as compared with that of 1990, tumors have been the second main cause of death just behind cardiovascular and cerebrovascular diseases, and the most common cancers are lung cancer, breast cancer, colorectal cancer, gastric cancer, liver cancer, cervical cancer, esophageal cancer, and bladder cancer. The authoritative survey data on the morbidity and mortality of various cancers in China in 2006 published on the tenth National Clinical Oncology Conference showed that the death toll of cancers was 3,000,000 in China in 2006, and there are approximately 2,120,000 newly confirmed cancer patients each year. In the mortality of malignant tumors, lung cancer ranks the first of the malignant tumors. Experts estimated that, by 2020, the death toll will exceed 4,000,000; by 2025, tumors will become the first major cause for the global death toll.
There are three means for clinically treating cancers, operation, radiotherapy and medical chemotherapy, antitumor drugs are the most commonly used therapy method, and the global market sale of antitumor drugs was 48 billion dollars in 2008. At present, clinical antitumor drugs are mainly classified into alkylating agent, antimetabolites, metal platinum, plant alkaloids and other natural drugs, cytotoxic antibiotics, etc. Platinum-based antitumor drugs were a sort of the most important antitumor drugs and were firstly developed in 1960s. The important differences from traditional cytotoxic antitumor drugs are an unique mechanism of action and an excellent antitumoral selectivity of platinum-based antitumor drug. Its main action target is DNA, which is cross-linked inter and intra DNA chains and forms platinum complex˜DNA composite, to disturb DNA replication or combines with nucleoprotein and plasmosin, belonging to a cycle nonspecific agent. Cis-dichlorodiamminoplatinum i.e., Cisplatin, cis-1,1-cyclobutanedicarboxylatodiamminoplatinum, i.e., Carboplatin, cis-glycolato-diamminoplatinum i.e., Nedaplatin, oxalato-(trans-L-1, 2-cyclohexanediamine) platinum i.e., Oxaliplatin, cis-[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl 1,3-dioxane](bidentate) platinum, i.e., Sunpla, and 1,2 diaminomethyl-cyclobutane-platinum lactate i.e., Lobaplatin etc. have been successfully developed in succession. Platinum-based antitumor drugs are characterized by a wide antitumor spectrum, a strong effect, etc. Moreover, the platinum-based antitumor drugs have a good synergistic effect with other antitumor drugs, which not only improves the inhabitation ratios of the existing tumors, but also expands the antitumor spectrum, thus consolidating the place of platinum-based antitumor drugs in clinical therapy. Hundreds of antitumor drugs were ranked by WHO in 1995, and cisplatin was ranked at the second place in comprehensive evaluations in terms of curative effects and markets. Statistical data indicates that, among all the chemotherapy schemes in China, 70%-80% are dominated by platinum or formulated with platinum-based drugs.
However, platinum-based antitumor drugs now have disadvantages of high toxicity such as myelosuppression, nephrotoxicity, nerve injury, etc., poor solubility, relatively narrow anticancer spectrum, and drug resistance, etc. Therefore, design and synthesis of new platinum-based antitumor drugs are now still one of the leading directions for the anticancer drugs research (M. A. Jakuper, M. Galanski, B. K. Keppler. Tumor-inhibiting platinum complexes-state of art and future perspectives, Rev. Physiol Biochem Pharmacol, 2003, 146, 1-53).
In recent two years, considerable studies have been conducted in order to reduce the toxic and side effects of platinum-based chemotherapy drugs, improve curative effects, reduce tumor recurrence and avoid to cause drug resistance, and improve the water solubility of the platinum compound. For example, the solubility of cisplatin is 2.65 mg/ml, the solubility of the followed Oxaliplatin is 7.9 mg/ml; the solubility of Carboplatin is 17.8 mg/ml; the solubility of Minoplatin is 27 mg/ml, and the toxic and side effects of Oxaliplatin and Carboplatin and the like are reduced as compared with those of cisplatin, the deficiency is that the solubility of the above so-called water-soluble platinum compound remains slightly soluble or sparingly soluble. Murray A. Plan et al prepared a sodium alcoholate salt for platinum compound, which effectively improved the solubility in vitro (U.S. Pat. No. 4,322,362A), but the compound must be just dissolved at pH of 10 or more and the toxicity problem was still not effectively solved. Giulia C et al also prepared a series of platinum compounds, however, the solubility of these compounds was still not remarkably improved (Chem Med Chem, 2009, 4(10), 1677-1685). WO2006091790A1 also disclosed a series of platinum compounds having specific structures, but similarly, the solubility problem and toxicity problem were still not successfully improved.